This is an application for a K01 award by Dr. Bryan D. James, an assistant professor and epidemiologist at the Rush Alzheimer's Disease Center (RADC). The overall goal of this K01 is to build a foundation of knowledge that will enable Dr. James to achieve his long-term goal of establishing himself as an independent investigator in the causes and prevention of cognitive decline in aging. The immediate goal, and the objective of the research application, is to understand how and why hospitalization leads to cognitive decline in some older persons. The award will supplement a strong background in epidemiologic methods and research ethics by providing Dr. James with the training necessary to fill gaps in his knowledge in three critical areas: 1) understanding clinical dementia and assessment of cognitive impairment in older adults, 2) expertise in using medical claims records for research, 3) comprehending the neurobiology and neuropathology of dementia. To achieve competence in these three areas, Dr. James has assembled a mentoring team of experts in complementary fields corresponding to these substantive areas. The primary mentor is Dr. Julie Schneider, the senior neuropathologist of the RADC, who has many years of mentorship experience and has served on and headed the NIA-N K committee. The other three mentors are Dr. David A. Bennett, a neurologist and the Director of the RADC; Dr. Robert S. Wilson, the RADC senior neuropsychologist and respected expert in the study of cognitive aging; and Dr. Raj C. Shah, a geriatrician and the medical director of the Rush Memory Clinic. In addition, Dr. James has assembled an Advisory Committee of experts in: critical care and cognitive impairment (Dr. E. Wesley Ely, Vanderbilt University), neurocritical care (Dr. Thomas Bleck, Rush University Medical Center), use of Medicare records for research (Dr. Jonathan Skinner, Dartmouth University), and neuroimaging (Dr. Konstantinos Arfanakis, RADC and Illinois Institute of Technology). The proposed research project will investigate cognitive decline after hospitalization in older adults; in particular, the prehospital risk factors (Aim 1), responsible hospital characteristics (Aim 2), and pathogenesis (Aim 3) of this phenomenon. The innovative study design will integrate longitudinal cognitive, clinical, neuropathologic, and neuroimaging data from a clinical-pathologic cohort of aging, the Rush Memory and Aging Project, with Medicare claims records providing detailed hospitalization information over more than a decade. Dr. James will leverage the existing data and infrastructure of the Memory and Aging Project and the existing 11 years of Medicare records previously obtained for this project. In addition, Dr. James proposes to obtain 6 more years of Medicare data from the Center for Medicare and Medicare Services (CMS). In Aim 1, Dr. James will examine the prehospital risk factors of accelerated cognitive decline after incident hospitalization and develop a risk profile for such decline. In Aim 2, he will examine the relationship of specific hospital characteristics with accelerated cognitive decline, including ICU stays, surgery, anesthesia, sepsis, and delirium. In Aim 3, he will investigate whether common neuropathologies of dementia, such as Alzheimer's disease and cerebrovascular disease, contribute to cognitive decline after hospitalization. The findings from this research will form the basis of an R01 grant application to the NIH before the end of the funding period.